Abstract T cells are mediators of the adaptive immune response. To properly mount a response, T cells use extracellular receptors to sense their environment and transduce signals to intracellular signaling networks. While many signaling pathways relevant to T cell function are established, less is known about how these pathways are modulated to discriminate between different types of signals and thus represents a significant gap in our knowledge base. Such knowledge would aid in controlling T cell activation and differentiation in multiple therapeutic settings. One dominant signaling input is T cell receptor (TCR) signaling strength, which regulates T cell differentiation, thymic development and cytokine signaling. In previous work, we identified that the strength of the T cell receptor signal differentially regulated the AKT/mTOR signaling axis. TCR signal strength regulated the phosphorylation of AKT which in turn controls AKT substrate specificity so that different TCR signal strengths engage qualitatively different AKT signaling networks. While these results are intriguing, the basic biochemical mechanisms that couple TCR signal strength to downstream signaling networks including differential AKT activation remains ill defined. One pathway that could couple TCR signal strength to intracellular signaling networks is phosphatidylinositol (PIP) metabolism. Many PIP species are bioactive and regulate signaling, transcription, metabolism and RNA splicing. Following pMHC binding to TCR, PI3K phosphorylates PI(4,5)P2 to generate PIP3 at the cell membrane. PIP3 has garnered interest because it activates kinases important for immune function, including AKT and PDK1. However, other bioactive PIP lipid species are generated and their functions in T cells are ill established. Based on a computational model we built to study the AKT activation in a T cell, our simulation unexpectedly predicted that different TCR signal strengths would generate different PIPs. Experimentally, we found that other bioactive PIPs in addition to PIP3 are generated at appreciable levels during T cell activation and that different TCR signal strengths generate different PIP species. Our proteomic screen identified proteins in a T cell that bind to specific PIPs, which positions us to identify novel pathways that are engaged during T cell activation. The novel result that T cells transduce TCR signal strength by generating different PIPs has the potential to illuminate a basic biochemical mechanism for how T cell interprets extracellular signals. These preliminary data serve as the basis of our central hypothesis that T cells encode TCR signal strength by generating different phosphatidylinositols to control T cell fate decisions, which will be tested by: 1) identifying mechanisms that control differential generation of phosphatidylinositols in response to TCR signal strength and 2) identifying how differential generation of phosphatidylinositols functions in the Treg versus T helper cell fate choice and the Th1 versus Th2 cell fate choice. Taken together, results from this work will provide novel mechanisms of receptor signal integration at the molecular level and identify functions of differential phosphatidylinositol generation in the context of CD4+ T cell fate choices.